Primary open angle glaucoma is a major cause of blindness. An elevated intraocular pressure (IOP) contributes to the pathogenesis of this disease. Glucocorticoids, given topically or systemically can elevate the IOP. In the proposed studies, we hope to understand the factors that determine the cellular sensitivity to glucocorticoids and to compare them in cells from normals and people with glaucoma. For these studies, cells in culture (skin fibroblasts, trabecular meshwork cells and peripheral blood lymphocytes) will be used. We also hope to undertake with the use of these systems a systematic study of the steroids that are direct glucocorticoid antagonists and of other factors that can blunt the cell's capability to respond to glucocorticoids. We will try to determine whether glucocorticoids, given systemically, to subjects with glaucoma, can acutely elevate the IOP. We will also try to see if blockade of endogenous glucocorticoid production will lower the IOP. It is hoped that these studies will provide a more rational basis for understanding whether it may be possible to affect the course of glaucoma by interfering with glucocorticoid production or action.